N-环己基-3-[[2-(3,4-二氯苯基)乙基]氨基]-N-[2-[[2-(3,4-二氢-5-羟基-3-氧代-2H-1,4-苯并恶嗪-8-基)乙基]氨基]乙基]丙酰胺 二(2,2,2-三氟乙酸盐)

IC50: 0.12 μM (SMYD2)

AZ505 ditrifluoroacetate is highly selective and shows an activity at submicromolar concentrations in vitro. The IC ₅₀ of AZ505 ditrifluoroacetate for SMYD2 is 0.12 μM, which is >600-fold greater than the IC ₅₀ s of AZ505 ditrifluoroacetate for other histone methyltransferases, such as SMYD3 (IC ₅₀ >83.3 μM), DOT1L (IC ₅₀ >83.3 μM) and AZ505 ditrifluoroacetate (IC ₅₀ >83.3 μM). AZ505 ditrifluoroacetate is a potent and selective SMYD2 inhibitor with an IC ₅₀ of 0.12 μM. The human SMYD (SET and MYND domain-containing protein) family of protein lysine methyltransferases contains five members (SMYD1-5). Moreover, AZ505 ditrifluoroacetate fails to inhibit the enzymatic activities of a panel of protein lysine methyltransferases. AZ505 ditrifluoroacetate is nominated for ITC binding study with K _d of 0.5 μM. In contrast, the calculated K _d for the p53 substrate peptide is 3.7 μM. AZ505 ditrifluoroacetate binding to SMYD2 is driven primarily by entropy, which often suggests that binding is mediated by hydrophobic interactions with few specific hydrogen bonds.